|
KMID : 0811720090130060475
|
|
Korean Journal of Physiology & Pharmacology
2009 Volume.13 No. 6 p.475 ~ p.482
|
|
|
Rifampicin Inhibits the LPS-induced Expression of Toll-like Receptor 2 via the Suppression of NF-?B DNA-binding Activity in RAW 264.7 Cells
|
|
Kim Seong-Keun
Lee Seong-Beom
Kim Young-Mi
Yeum Chung-Eun
Jin Song-Hyo
Chae Gue-Tae
|
|
|
Abstract
|
|
|
|
Rifampicin is a macrocyclic antibiotic which is used extensively for treatment against Mycobacterium tuberculosis and other mycobacterial infections. Recently, a number of studies have focused on the immune-regulatory effects of rifampicin. Therefore, we hypothesized that rifampicin may influence the TLR2 expression in LPS-activated RAW 264.7 cells. In this study, we determined that rifampicin suppresses LPS-induced TLR2 mRNA expression. The down-regulation of TLR2 expression coincided with decreased production of TNF-?. Since NF-?B is a major transcription factor that regulates genes for TLR2 and TNF-?, we examined the effect of rifampicin on the LPS-induced NF-?B activation. Rifampicin inhibited NF-?B DNA-binding activity in LPS-activated RAW 264.7 cells, while it did not affect IKK?/? activity. However, rifampicin slightly inhibited the nuclear translocation of NF-?B p65. In addition, rifampicin increased physical interaction between pregnane X receptor, a receptor for rifampicin, and NF-?B p65, suggesting pregnane X receptor interferes with NF-?B binding to DNA. Taken together, our results demonstrate that rifampicin inhibits LPS-induced TLR2 expression, at least in part, via the suppression of NF-?B DNA-binding activity in RAW 264.7 cells. Thus, the present results suggest that the rifampicin-mediated inhibition of TLR2 via the suppression of NF-?B DNA- binding activity may be a novel mechanism of the immune-suppressive effects of rifampicin
|
|
|
KEYWORD
|
|
|
Rifampicin, TLR2, LPS, Pregnane X receptor, NF-?B
|
|
|
FullTexts / Linksout information
|
|
 
|
|
|
Listed journal information
|
|
  
|
|